The goal of the SPORE in Prostate Cancer at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University has been to bring together multidisciplinary investigators dedicated to conducting state of the art translational research on prostate cancer to develop and test interventions that improve the outcome of patients with prostate cancer. In this renewal application, we bring together investigators at Northwestern University, Evanston Northwestern Healthcare and the University of Chicago. The 5 research projects are: 1) Adoptive transfer of tumor-reactive TGF-p insensitive CD8+ T cells for the treatment of patients with advanced prostate cancer- a translational clinical intervention study (Lee and Kuzel). 2) 5-Alpha-reductase inhibition in intermittent androgen ablation therapy of prostate cancer (Wang and Shevrin). 3) Prostate cancer-dependent generation of angiostatin 4.5 (Soff and Kuzel). 4) Radiation inducible TNF-alpha therapy in prostate cancer (Weichselbaum and Stadler) and 5) Modulation of transforming growth factor p-dependent motility in prostate cancer by the chemopreventive agent genistein (Bergan and Catalona). These projects represent a balanced approach to prostate cancer research, including prevention (Project 5), localized disease (Project 4), androgen sensitive prostate cancer (Project 2), hormone refractory disease (Project 3) and metastatic cancer (Project 1). The SPORE Program also has highly structured Developmental Research and Career Development Programs. The above Projects and Programs are supported by 4 cores: the Administrative Core, the Biostatistics/Bioinformatics Core, the Specimen Procurement Core, and the Clinical Trials and Advocacy Input/Outreach Core. These cores provide efficient leadership and infrastructure to facilitate SPORE specific research. The Internal and External Advisory Committees evaluate program progress and offer guidance to the SPORE Director. These committees empower the Program Director, Co-Director and the Executive Committee the flexibility to quickly respond to new research opportunities. With a large patient population and a successful track record, the proposed SPORE program is poised to meet the challenge of the 21 century in prostate cancer research.